While data regarding the reproductive safety of certain
psychotropics such as selective serotonin reuptake inhibitors and
anti-epileptic drugs have increased over the last several years,
information regarding attendant risks of fetal exposure to
antipsychotics remains more sparse.

This is particularly true for the newer atypical antipsychotics,
which are increasingly being used in women of reproductive age for a
range of psychiatric disorders in addition to schizophrenia, including
bipolar disorder and depression.

It is therefore critical that clinicians and women have good
information upon which to base decisions about continuing treatment
during pregnancy. There are several decades' worth of data from
large studies supporting the reproductive safety of the typical
antipsychotics such as haloperidol or thiothixene, but the reproductive
safety data for the atypical antipsychotics are extremely sparse.

To date, few prospective studies on atypicals in pregnant women
have been published. In a study comparing pregnancy outcomes in 151
subjects exposed to different atypicals--60 to olanzapine, 49 to
risperidone, 36 to quetiapine. and 6 to clozapine--with nonexposed
controls, major malformation rates were not significantly different
between the two groups (J. Clin. Psychiatry 2005;66:444-9). However,
this is a relatively small sample. (The other two atypicals available
are aripip-razole and ziprasidone.)

The other available safety data on atypical antipsychotics in
pregnant women are derived mainly from case reports or small case
series, which have not identified an increased risk for major
malformations.

Most of the prospectively identified cases of exposure are to
olanzapine (133), risperidone (over 500), and quetiapine (42), with very
few to aripiprazole and clozapine, and possibly none to ziprasidone. In
March, some of the first registry data on atypicals were reported at a
meeting, from the Australian Pregnancy Registry. Among 38 pregnancies
exposed to atypical antipsychotics, there were no major malformations.

The association of the atypicals with weight gain, diabetes, and
hypertension raises another potential safety issue when these drugs are
used during pregnancy. Weight gain and adiposity in pregnant women have
also been associated with an increased risk of neural-tube defects,
independent of folate status (Am. J. Psychiatry 2002;159:136-7).

As is often the case when considering the use of psychotropics
during pregnancy, the specific clinical approach depends on when the
patient sees the clinician.

For a patient who presents for evaluation before pregnancy on a low
dose of an atypical antipsychotic as an adjunct to a mood stabilizer, it
may make sense to switch to an antipsychotic for which more reproductive
safety data are available, such as perphenazine. This scenario may not
always be feasible, however, because many patients present when they are
already pregnant. If they are well maintained, the clinician may be
understandably reluctant to make changes.

Because of the absence of indicting data, we have typically
maintained patients on atypical antipsychotics if they are already
pregnant because of our concerns about clinical destabilization.
However, we do recommend close follow-up for safety issues such as
weight gain, diabetes, and hypertension during pregnancy, working
collaboratively with the obstetrician. Another consideration is that,
although there are no robust data clearly distinguishing differences in
efficacy, there are patients who appear to derive particular benefit
from an atypical antipsychotic.

Based on the limited data available, there does not appear to be a
glaring reproductive safety signal for the atypicals. But given the
prevalence of use of these medicines in psychiatry, we clearly need more
quality data on this drug class, similar to those we have for
antidepressants and antiepileptic drugs (AEDs), so that that the
atypicals can be safely integrated into the treatment algorithms used
during pregnancy to treat women across that spectrum of disease states.

We are establishing an atypical antipsychotic pregnancy registry at
Massachusetts General Hospital that will be similar to the North
American AED registry. This registry, along with other global AED
registries, has produced invaluable data on the reproductive safety of
antiepileptics.

We hope that data from registries and studies on atypical
antipsychotics will be collected in a timely fashion and will make it
possible for women and their physicians to make more informed decisions
about use of this class of medicines during pregnancy.

BY LEE COHEN, M.D.

DR. COHEN directs the perinatal psychiatry program at Massachusetts
General Hospital, Boston, which provides information about pregnancy and
mental health at www.womensmentalhealth.org. He is a consultant to
manufacturers of atypical antipsychotics.

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